This is a collaborative multi-disciplinary program involving investigators at the Massachusetts Institute of Technology and the New England Eye Center. Optical Coherence Tomography (OCT) is an emerging technology for ophthalmic performance that can perform non-contact, non-invasive real time cross sectional imaging of the retina and the anterior eye. Standard ophthalmic OCT has a 10 micron axial resolution, ten times higher than conventional ultrasound. Our objective is to develop new OCT technology, which achieves a quantum leap in performance over current ophthalmic OCT and to demonstrate this technology for the early diagnosis and monitoring of disease of the retina and anterior eye. We will increase OCT axial image resolution by 5 to 10 times from 10 microns to about 1-2 microns. And also develop multi-wavelength, spectroscopic OCT techniques to improve differentiation of morphology and permit micron scale functional imaging. Our hypothesis is that these advances will dramatically enhance ability to image structural morphology such as intraretinal features, as well as improve the accuracy in reproducibility of morphometric measurements such as retinal thickness or nerve fiber layer thickness. We propose to: 1. Develop ultra high resolution OCT technology for imaging the retina and anterior eye. 2. Image transgenic retinal mouse models and cross sectional and longitudinal studies. 3. Perform cross sectional patient studies to investigate the capabilities of ultra-high resolution OCT for identifying micro-structural changes associated with posterior segment diseases. 4. Investigate ultra high resolution OCT for improving the accuracy of morphometric imaging of retinal thickness and nerve fiber layer thickness. 5. Investigate imaging structures in the anterior eye at the cellular level. 6. Perform preliminary clinical studies to investigate the ability of ultra high resolution OCT to identify ocular pathologies in the anterior eye segment. 7. Develop and demonstrate spectroscopic OCT techniques enabling spectrally resolved tomographic imaging on the micron scale. 8. Demonstrate spectroscopic OCT imaging of oxygen saturation in retinal and choroidal vasculature. 9. Perform preliminary clinical studies to assess the effectiveness of ultra high resolution structural, morphometric, or spectroscopic OCT imaging to diagnosis and monitor the progression of retinal disease. This proposal involves the development of new instrumentation which will have wide spread research and clinical applications as well as the development and validation of methods for the early diagnosis and monitoring of diseases including AMD, glaucoma, and diabetic retinopathy.